Suicide is the second leading cause of death among adolescents. While clinicians and researchers have begun to recognize the importance of considering multidimensional factors in understanding risk for suicidal thoughts and behaviors (STBs) during this developmental period, the role of puberty has been largely ignored. In this review, we contend that the hormonal events that occur during puberty have significant effects on the organization and development of brain systems implicated in the regulation of social stressors, including amygdala, hippocampus, striatum, medial prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex. Guided by previous experimental work in adults, we also propose that the influence of pubertal hormones and social stressors on neural systems related to risk for STBs is especially critical to consider in adolescents with a neurobiological sensitivity to hormonal changes. Furthermore, facets of the pubertal transition, such as pubertal timing, warrant deeper investigation and may help us gain a more comprehensive understanding of sex differences in the neurobiological and psychosocial mechanisms underlying adolescent STBs. Ultimately, advancing our understanding of the pubertal processes that contribute to suicide risk will improve early detection and facilitate the development of more effective, sex-specific, psychiatric interventions for adolescents.

Suicidal ideation (SI) and non-suicidal self-injury (NSSI) are two distinct yet often co-occurring risk factors for suicide deaths in adolescents. Elucidating the neurobiological patterns that specifically characterize SI and NSSI in adolescents is needed to inform the use of these markers in intervention studies and to develop brain-based treatment targets. Here, we clinically assessed 70 adolescents-49 adolescents with depression and 21 healthy controls-to determine SI and NSSI history. Twenty-eight of the depressed adolescents had a history of SI and 29 had a history of NSSI (20 overlapping). All participants underwent a resting-state fMRI scan. We compared groups in network coherence of subdivisions of the central executive network (CEN), default mode network (DMN), and salience network (SN). We also examined group differences in between-network connectivity and explored brain-behavior correlations. Depressed adolescents with SI and with NSSI had lower coherence in the ventral DMN compared to those without SI or NSSI, respectively, and healthy controls (all ps < 0.043, uncorrected). Depressed adolescents with NSSI had lower coherence in the anterior DMN and in insula-SN (all ps < 0.030, uncorrected), and higher CEN-DMN connectivity compared to those without NSSI and healthy controls (all ps < 0.030, uncorrected). Lower network coherence in all DMN subnetworks and insula-SN were associated with higher past-month SI and NSSI (all ps < 0.001, uncorrected). Thus, in our sample, both SI and NSSI are related to brain networks associated with difficulties in self-referential processing and future planning, while NSSI specifically is related to brain networks associated with disruptions in interoceptive awareness.